Hemosep
®
Life changing technology...
S u r g i c a l
www.advancissurgical.com
Contents
Overview
Page 2
General description of the Hemosep® device
Page 2
Mechanism of action for the Hemosep® device
Page 3
The Hemosep® bag
Page 3
The blood collection bag
Page 4
Intended clinical performance
Page 4
Design calculations
Page 4
Pre-clinical testing- non clinical performance studies
Page 4
Bovine blood tests
Page 5
Studies with human blood
Page 6
Clinical outcome of transfusion processed by ultrafiltration
in patients undergoing coronary bypass
Page 8
Cardiac application
Page 10
Intra Operative application
Page 11
Frequently asked questions
Page 12
1.
Overview
A number of technologies have evolved to fulfil the haemoconcentration task over the past decades. These include the use of modified
dialysis technology and more commonly, the use of centrifuge devices to concentrate cell populations and remove excess water and
plasma*1,2,3. These devices are fairly complex in nature and require specialist technical knowledge to operate. In addition, such devices
produce both a concentrated blood product and a liquid waste effluent which may represent a contamination risk. These techniques are
however considered to be an increasingly important part of modern practice, particularly as blood used during such operations has a
significant cost and there remains a risk of transfusion associated infection and reaction if donor rather than autologous blood is utilised.
The object of the Hemosep® development was to design a haemoconcentration technology that produces a blood concentrate in all
cell species, maintaining not only the RBC’s but preserving the platelets, WBC’s and clotting residuals and does not require
centrifugation and associated blood transfer steps and can be utilised without the need for highly trained technical personnel. In
answering this challenge, the Hemosep® concept was developed, based upon the use of a membrane controlled superabsorber
driven plasma removal process. This process is carried out entirely in one vessel and requires no additional blood transfer steps or
flushing procedures. In essence the Hemosep® device is a one-stop haemoconcentration process for concentrating residual blood
from the blood reservoir during surgery. Residual blood is introduced into the device, concentrated using the membrane controlled
superabsorber process, and transfused back to the patient using a transfer bag, saving all cell species.
An additional benefit of the Hemosep® technology is that it produces a gelatinous waste product, essentially plasma in a gel matrix,
which is safer and easier to dispose of than the large volumes of fluid associated with the more common centrifugation processes.
2.
4.
3.
5.
1.
Fig: 1.The Hemosep® technology: 1.The Hemosep® bag, 2. Hemosep® Shaker, 3.The blood collection bag, 4. Blood reservoir and 5. Suction tool.
General description of the Hemosep® device
The Hemosep® device concentrates blood by removing the fluid component of whole blood, the plasma, from a pooled volume of blood
salvaged during, or at the end of surgery. The technique for removing the plasma from the blood product, leading to concentration of
the cellular components, is fairly simple but involves a number of critical steps and controls.
The Hemosep® system consists of 4 major components (fig. 1):
1.
The Hemosep® bag (1)
2.Hemosep® Shaker Unit (2)
3.
A blood collection bag for the collection of processed blood (3)
4.
Intra operative pump, suction and blood reservoir (4,5)
2.
Mechanism of action for the Hemosep® device
The Hemosep® device relies upon two main constituent elements
for its primary function of concentrating blood cells from
haemodiluted media. These components are the control membrane
and the superabsorber, the other elements of the device are
designed to simply contain the blood prior to and during processing
and to contain plasma removed from the blood product. In use
haemodiluted blood is transferred via the suction tool into the
blood reservoir and then pumped into the Hemosep® device.
The blood is separated from a superabsorber pad by a control
membrane with a pore size which prevents the migration of
cellular species from the blood into the superabsorber section of
the device. Free passage of the plasma however is not restricted
and as this fluid passes from the blood through the membrane
into the superabsorber, it results in a concentration of the cellular
components of the blood held within the bag. Once the appropriate
level of haemoconcentration is achieved (normally a packed cell
volume in excess of 33%), the blood held in the bag is transferred
into a transfer bag for subsequent transfusion to the patient.
Fig: 2.Typical size range for blood cells. Note the platelets, the
smallest of the blood cells, are typically 2-3 microns in size.
The Hemosep® bag
The Hemosep® bag element of the system is the active processing section of the device. It consists of a blood bag with a filter
membrane bag suspended within it, within which is a sheet of superabsorber material. The filter membrane material employed in the
device has a unique size pore structure.
The filter membrane is the control membrane of the system and the unique pore size for this important element of the device has been
selected to ensure that no cellular components of the blood product can pass into the superabsorber during use. The unique pore size
is small enough to permit efficient fluid transport into the superabsorber but is too restrictively small to permit the passage of cells,
even the smallest intact cells, the platelets (fig. 2).
Fig: 3. Hemosep® bag seen within the bag chamber positioned on
top of the Hemosep® device.This placement of the bag within this
chamber prevents manual manipulation of the device during blood
processing.
Fig: 4.The plasma which passes across the control membrane into
the superabsorber forms a gelatinous matrix which cannot pass
back into the blood reservoir.The matrix can be seen here as a
yellow gelatinous material in the centre of the device.
3.
The blood collection bag
The blood collection bag is a simple blood bag which is connected to the outlet
of the Hemosep® bag after blood processing and into which the processed
blood is drained (fig. 5).
Intended clinical performance
The Hemosep® device is intended to concentrate the residual blood during and
after the operative procedure. This blood is highly haemodiluted and if returned
to the patient in its raw state, may lead to excessive bleeding and patient
haemodilution in the critical post surgical recovery phase. Concentration of this
blood product to near-normal cell concentrations (PCV level 33 - 45%) renders Fig: 5.The blood collection bag
it suitable for re-transfusion and diminishes the bleeding risk of unprocessed
blood. The transfusion of the processed autologous blood reduces the need for donor blood products and their associated transfusion
reactions. The Hemosep® device, under normal clinical conditions, is intended to concentrate residual blood from low PCV’s (20% or
less) to near-normal levels (at least 33%) without the need for centrifuge technology.
Design calculations
The Hemosep® device is designed to concentrate the residual blood in surgery. The volume of this blood can vary significantly, but is
generally in the region of 750ml depending on the amount re-transfused to the patient. The Hemosep® device is therefore designed to
meet these requirements and has a capacity of up to 1 litre. The design of the control membrane reflects the need to spare a broad
range of cellular species from the smallest platelets to larger white cell species (3-20microns). A unique pore size was selected for this
element of the device to meet this need, but it is recognised that some platelets may be lost in processing due to deformation of the
cell structure in interaction with the pores.
Fig: 5a.The final design of the Hemosep®
concentrator bag
The amount of superabsorber incorporated into the device was derived from
the required performance characteristics to ensure that there is sufficient
material for adequate concentration and also to make sure that there is no
possibility of superabsorber saturation. This might lead to superabsorber
migrations from the inner vessel through the control membrane and into the
blood product. With a maximum of 1 litre capacity at a PCV of 20% (extreme
clinical conditions), there is 640ml of plasma present in the blood product.
Our assessment of superabsorber capacity confirms that the superabsorber is
capable of absorbing 234ml of fluid per gram of material. Only in the region of
3g of superabsorber material is required to absorb all of the plasma present.
However, to ensure that there is no possibility of the superabsorber transferring
from the inner to outer chambers, in other words to ensure unidirectional
flow of the fluid, 15g of superabsorber materials is employed in the Hemosep®
product. This mass of superabsorber is capable of absorbing up to 3 litres of
fluid and represents a considerable margin for safety in the device (fig.5a).
Pre-clinical testing - non clinical performance studies
Early performance tests of the Hemosep® device were performed using fresh heparinised bovine blood with haematocrit adjusted with
saline solution to match common clinical values. In addition to testing the performance of the device with bovine blood, tests were
carried out using freshly donated human blood to confirm the function of the device under near-clinical conditions.
4.
Bovine blood tests
Fresh heparinised bovine blood was diluted using saline to a packed cell volume (PCV) of 20%. A 500ml volume of blood was then
injected into the Hemosep® device after the device had been wetted and activated with 200ml of saline. The blood was then left to
incubate in the Hemosep® device for a period of 40 minutes. Blood samples were taken from the device at 5 minute intervals and the
PCV measured using centrifugation (fig. 6).
Level of Blood Concentration Achieved in Passive Mode
Fig: 6 Effect of passive incubation on packed cell volume (PCV) in fresh heparinised bovine blood haemodiluted to 15%. The clinical target level of
PCV (35-40%) was achieved in around 15 minutes.
In an effort to reduce the processing speed of the device, the addition of an agitation step was introduced. The agitation was provided
by placing the blood filled Hemosep® device onto an orbital shaker platform, operating at 120 cycles per minute. This additional process
reduced the blood processing time (time to reaching desired clinical values) by up to 30% (fig. 6a).
Effect of Exposure Time on PCV of Whole Blood with Optimal Device Configuration With Agitation
Fig: 6a. Effect of active incubation on packed cell volume (PCV) in fresh heparinised bovine blood haemodiluted to 15%.The clinical target level of
PCV (35-40%) was achieved in around 10 minutes.This represents a significant reduction in processing time which may be important in the clinical
setting.
Through these bovine blood studies a number of factors were clarified:
1.
The device was shown to function very well in terms of raising the PCV of haemodiluted blood products to acceptable clinical levels.
2.
The addition of agitation during the concentration step reduced the processing time, most likely by effectively scouring the control membrane surface with blood during processing, resulting in the maintenance of pore patency.
5.
Studies with human blood
50
Haematocrit
(%) (%)
Haematocrit
Similar studies to those carried out in bovine blood were
performed on fresh heparinised human blood by the National
Blood Service, Brentwood, Essex*4. The focus of these studies
was to determine whether the results obtained from the study
of the Hemosep® device with bovine blood was reflected in
studies with fresh human blood. Although there is little by way
of cell size difference between bovine and human blood, there is
always a possibility of inter-species differences in terms of testing
a novel medical device. These studies utilised a fixed processing
time and orbital shaker driven agitation at 120 cycles per minute
respectively. The human blood studies went into considerable
detail with regard to the overall biocompatibility of the Hemosep®
device, however, a summary of the results of the cell processing
performance is shown in fig. 7.
***
40
30
20
10
0
Pre
Pre
Post
Post
Fig: 7. Rise in haematocrit (PCV) in human blood over the processing
time. In all cases the PCV increased from 20% to within normal limits
(36-50%). Data taken from National Blood Service Report.
This data, taken from the study of human blood match very well with that derived from bovine studies. A similar outcome was
apparent in the analysis of platelet survival rates when the Hemosep® device was employed with human blood (fig. 8a & 8b).
Fig:8b
Platelet count (x109/L)
Platelet count (x109/U)
Fig:8a
Pre
Post
Pre
Post
Fig: 8a & 8b. Analysis of the effect of blood processing with the Hemosep® device on platelet numbers. Fig: 8a demonstrates that the device raises
platelet numbers from sub-normal levels to within the normal range over the processing period. Fig: 8b, platelet count per blood unit, shows that
there is a net loss of platelets during processing, but this does not impact upon the normalisation of the platelet count associated with processing.
Overall the results derived from the human blood trials mimicked those obtained from the study of bovine blood. Both studies show
that the Hemosep® device:
•
Concentrates haemodiluted blood, raising PCV from sub-normal levels to normal clinical levels.
•
The use of the device, incorporating the unique control membrane, results in concentration of platelets from sub-normal levels to normal clinical levels.
In addition to these findings with regards to the basic function of the Hemosep® device, the National Blood Service report
confirmed that the device was not associated with haemolysis and increased white cell populations to normal clinical values.
6.
The Hemosep® bag is the active processing section of the
device and consists of three parts:
1.
2.
All blood cells maintained
3.
Filtered element including plasma
1.The blood bag - This houses the technology (the filter membrane and the super absorbent pad) and blood whilst it is filtered.
2. Filter membrane - This has a unique pore structure to control what is able to pass through during filtration so that no cellular components can pass into the super absorbent pad.
3. Super absorbent pad - This absorbs all unwanted blood product during the filtration in the filter membrane and turns them into a gel like substance for easy disposal once complete.
7.
Clinical outcome of transfusion processed by
ultrafiltration in patients undergoing coronary bypass
Abstract
Terence Gourlay- Bioenginering Unit, University of Strathclyde-UK
Serdar Gunaydin- University of K. Kale, Turkey
Objective
Following termination of cardiopulmonary bypass (CPB), the circuit contains a significant volume of diluted blood and various methods
have been used to salvage this blood including direct transfusion or centrifugation/washing of the circuit volume. We designed a
prospective clinical trial to determine the clinical outcomes of transfusion of autologous blood processed by a novel ultrafiltration
device (Hemosep® Advancis Surgical, Nottingham, UK) in high risk patients undergoing coronary re-vascularization.
Patients & Methods
Over a 6-month period, 40 high risk patients (Euroscore 6+) undergoing CABG with full heparin dose strategy were prospectively
randomised into 2 equal groups (N=20). In group 1, following the cessation of CPB, salvaged blood in the venous reservoir was pumped
into the Hemosep® bag until the desired volume has been introduced and processed for re-transfusion back to the patients. Group 2
patients were controlled and this technology was not employed. Blood samples were collected at baseline (T1); at the end of the CPB
(T2) and 24 h (T3), postoperatively.
Comparison with patient’s pre-operative blood
White Cell Count
Platelet Count
Haematocrit
Haemoglobin
Pre Surgery
Post Hemosep®
%Change
6.71 +/- 0.63
198636 +/- 31101
43.5 +/- 1.9
12.14 +/-1.51
13.8 +/- 1.9
192650 +/- 34906
39.45 +/- 2.1
12.83 +/- 0.85
105.6
-3.4
-9.3
5.6
Effect of Hemosep® device on cell populations and haemoglobin. Comparison of pre-surgery and post-Hemosep® blood samples. All factors were
within 10% of “normal” pre-surgical levels with the exception of white cell counts which were almost double the baseline levels in these patients.
This is probably the result of well documented white cell dynamics associated with the deployment of cardiopulmonary bypass.
36.90%
35
29.50%
30
22.50%
mm -3
%
25
20
10
5
2
Blood Count and PCV
8.80
8
4
0
146.00
150
110.00
100
50
Baseline
60% increase in PCV, 62% increase in WBC, 32%
increase in platelets
Results
193.00
200
11.40
12
10
15th Minute 40th Minute
14.20
14
6
Baseline
250
16
15
0
Fig 9C - Platelet Count
1000mm-3
40
Fig 9B - WBC
normal cell range
Fig 9A - Haematocrit Levels
15th Minute 40th Minute
0
Baseline
15th Minute
40th Minute
Results
Hemosep® 66% increase in HGB, 62% increase in
WBC, 32% increase in platelets
Mean processed blood was 775±125mL.80% (N=16) patients in group 1 and 30% (N=6) in control group did not receive any bank
blood (p<0.05). Postoperative bleeding was 545±180 cc in group 1 versus 725±200 cc in control (p<0.05). IL-6 levels (pg/ml) were
significantly lower in group 1 versus control at T3 (11±4 versus 32±8; p<0.05). CD11b/CD18 levels (%) were significantly lower in group
1 (14±4) versus control (23±8) at T3 (p<0.05).
8.
Effect of Hemosep® device on cell populations and haemoglobin. Comparison of pre- and post- Hemosep®
blood samples
White Cell Count
Platelet Count
Haematocrit
Haemoglobin
Pre Hemosep®
Post Hemosep®
%Change
10.97 +/- 0.98
148800 +/- 23841
22.5 +/- 1.6
7.78 +/- 1.02
15.78 +/- 1.5
173272 +/- 79786
38.45 +/- 2.7
11.45 +/- 1.05
43.6
16.4
70.9
47.2
Hemosep® (N=52)
Control (N=50)
P
545±180
725±200
>0.05
1±0.8
0.95±1.2
2.4±1
2.4±3
<0.05
>0.05
73% (38 pts)
38% (19 pts)
<0.05
Results clinical follow up
Postoperative Bleeding
(24 h) (cc)
RBC Transfusion (Unit)
FFP Transfusion (Unit)
Patients with no Transfusion
(%)
Conclusions
Use of the Hemosep® device for salvaging blood is associated with significant decrease in post-CPB inflammatory response,
postoperative bleeding and the need of transfusion with prevention of exposure to expensive and precarious allogeneic blood products.
Residual ECC blood was also analysed with respect to:
Serum Albumin Levels
Factor V11 Levels
Serum fibrinogen levels
IL-6 Levels
9.
Cardiac application
For some decades now, clinicians have employed Haemoconcentration, either during the operative procedure, or more commonly on
the residual blood left in the CPB system at termination of CPB to concentrate the blood cells prior to re-administration to the patient.
These include the use of modified dialysis technology and more commonly, the use of centrifuge devices to concentrate cell populations
and remove excess water and plasma.
The Hemosep® device can be utilised to ultra-filtrate this residual blood following termination of the CPB system. This approach
reduces the need for donor blood and blood associated products therefore reducing the risks associated with it.
To collect the blood left in the heart lung machine, simply
connect the concentrator bag with the leur lock connection
to the tubing below the reservoir for gravity fill applications,
or connect to the tubbing above the reservoir and pump the
blood into the concentrator bag, as shown in the diagram to
the right.
Connect to top
of reservoir for
pump fill
Left: Hemosep® bag connecting into the CPB system for pump/
gravity fill
Use Leur lock
connection
Connect to bottom of reservoir for gravity fill
Patient Features and Benefits
• Patient’s own blood is transfused, reducing the risk of contamination and reaction
• Decreased need for donor blood and associated transfusion products, leading to a reduction in donor dependency
• Assists in the reduction of post-operative bleeding, resulting in improved patient recovery
• Maintenance of platelet population means there is preservation of normal clotting function
• Reduction in inflammatory molecules, resulting in a reduction in post-operative complications
10.
Intra operative application
Further developments of the Hemosep® device has resulted in an intra operative option with the addition of a heparin infused suction
tool. The device is capable of aspirating blood from the surgical site directly into a blood reservoir, this can be filled up to a volume of
1000ml and then pumped directly into the Hemosep® concentrator bag for processing of the blood. It is still possible to continue with
the suction of fluid from the surgical site while the concentrator bay is being shaken on the device.
The use of the Hemosep® intra operative device presents a wealth of application
possibilities, with the inclusion of the Intra Operative suction tool and blood
reservoir the device could be used during most blood loss procedures.
Using the unique ultrafiltration technique the device is able to effectively produce
a high quality blood product in order to aid the patient recovery time and
dramatically reduce the need for donor blood and associated products.
Hemosep® intra operative can give health care professionals flexibility of use
by utilising the suction capabilities of the device and assessing the appropriate
direction to either filter the blood or disregard the fluid and take other action.
This flexible approach is achieved by packing the Hemosep® consumables in
separately sterilized packaging and making them available via different ordering
codes. By designing the device in this way Advancis Surgical are able to increase
your flexibility and help control surgical costs.
Aspirate directly from the surgical site and pump from
the reservoir into the concentrator bag
The Hemosep® consumables consists of:
1. The concentrator and blood bag
CR4111
2. The suction tool and wand
CR4334
3. The blood reservoir and
internal pump
CR4339
11.
Frequently asked questions
How is leukocyte activation managed?
Leukocyte activation is not a real problem post-CPB.The leukocyte dynamics associated with CPB result in a high leukocyte population, but
these are largely in an inactivated state. If health care professionals are concerned about the leukocyte population of the concentrate, they may
choose to leukocyte filter the material. Some clinical groups leukocyte filter all blood products as a matter of course.The view of many health
care professionals is that this should not be necessary.
Will the Hemosep® device aid in the reduction of post-operative bleeding?
Post-operative bleeding is a major factor in any major surgery, there are several factors surrounding the cause of this. One factor is the
reduction in clotting factors associated with the current practice of only giving a patient back the red blood cells, therefore reducing the
clotting agents in the blood and the Hemosep® device.The Hemosep® device recycles the blood in all cell species, retaining the residual
clotting factors in the concentrate; this in turn will aid in the reduction of post-operative bleeding and potential help in the reduction of surgery.
Postoperative Bleeding (24 h) (cc)
Hemosep® (N=52)
Control (N=50)
DIF
545±180
725±200
33%
Are there any other areas the device can be used in?
Advancis Surgical will be developing additions to the device for use in the Orthopaedic, Paediatric and Neonatal practices.
I currently have a contract for cell salvage devices, how can I justify the purchase of this product for my trust?
Due to the way Hemosep® recycles the cell species, it saves money by reducing the need to add platelets to a patient (the cost of platelets
are £209.30 per bag with an average 1.2 bags being used per patient transfusion). Hemosep® can save around £150 per patient, making it
economical even if current cell salvage techniques are still in place.
Will Hemosep® remove any damaged RBC, WBC cells as with the Cell Saver device?
The Hemosep® device will remove fragmented cells and fragments below the pore size.
What is the overall quality of blood returned to the patient post CPB?
The blood product returned after concentration is very similar to that of the pre-surgical blood.
White Cell Count
Platelet Count
Haematocrit
Haemoglobin
Pre Hemosep®
Post Hemosep®
%Change
10.97 +/- 0.98
148800 +/- 23841
22.5 +/- 1.6
7.78 +/- 1.02
15.78 +/- 1.5
173272 +/- 79786
38.45 +/- 2.7
11.45 +/- 1.05
43.6
16.4
70.9
47.2
Do you have details of the effect of the activated platelet levels and any potential issues surrounding it?
There is no suggestion at the present time that platelets are activated by the process.
How much heparin is left in the processed blood?
The levels of heparin left in the processed blood are negligible, when transfused back to the patient the systemic levels are within the same
scope as levels needing to be achieved when heparin is administered, it is therefore not necessary to increase the protamine levels, in cases
where several bags of blood are transfused back to the patient it is advised to monitor the A.C.T. and take appropriate action.
In which surgical procedure is Hemosep® best suited?
Hemosep® is best suited to elective producers where a steady blood loss occurs; in cases of massive trauma many centres will adopt the
practice of returning the whole blood to the patient in order to give the blood back as quickly as possible. Standard cell saver devices can be
used to accomplish this, however in the case of massive trauma there is little evidence to suggest there is any clinical benefit to the patient.
What are the benefits of returning the white blood cells (WBC)?
The WBC are in a nonactivated state therefore classed as fresh WBC’s, these are essential to fighting infections in the body and should
therefore aid in the overall recovery period.
Assessment of platelet activation and overall quality
This is yet to be investigated fully but there is no reason to assume that platelet function will be impacted by the use of the technology.There is
no high sheer during the process and surface contact is minimal. Small platelets and platelet fragments are removed by the system, resulting in
a loss of around 30% of platelet numbers.These studies are underway, however our clinical studies suggest that there is a reduction in the need
for platelets post-surgery.
12.
References
1. Delaney E, Rosinski D, Ellis H, Samolyk KA, Riley JB. An in-vitro comparison between Hemobag and non-Hemobag ultrafiltration methods of salvaging circuit blood following
cardiopulmonary bypass. J Extra Corpor Technol. 2010 Jun;42(2):128-33
2. Johnson HD, Morgan MS, Utley JR, Leyand SA, Nguyen-Duy T, Crawley DM. Comparative analysis of recovery of cardiopulmonary bypass residual blood: cell saver vs
haemoconcentrator J Extra Corpor Technol. 1994 Dec;26(4):194-9
3. Nakamura Y, Masuda M, Toshima Y, Asou T, Oe M, Kinoshita K, Kawachi Y, Tanaka J, Tokunaga K. Comparative study of cell saver ultrafiltration nontransfusion in
cardiac surgery. Ann Thorac Surg. 1990 Jun;49(6):973-8.
4. NHS Blood & Transplant Biocompatibility Blood Testing Report Ref: MINI/CD/2011- FINAL V2 - BW Ref:TR-111 for full report
5. Blood transfusion and the Anaesthetist Blood Compartment Therapy 2005
6. Catalyst-health-the-increasing-cost-of-blood-transfusions. NHSBT hospital. Blood price_list_2012_2013.pdf
7. Prices for blood, blood components and diagnostic services for 2004/2005, Prof. Lindsey Davies, Regional Director of Public Health at the Department of Health and Social Care
,
:
:
: f
MAR238/r2
,
S u r g i c a l
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